Vaccines

18 pages, 1585 KB

Open AccessEditor’s ChoiceReview

Understanding Vaccine Hesitancy: Insights and Improvement Strategies Drawn from a Multi-Study Review

by Kaitlin (Quirk) Brumbaugh, Frances Gellert and Ali H. Mokdad

Vaccines 2025, 13(10), 1003; https://doi.org/10.3390/vaccines13101003 - 25 Sep 2025

Cited by 15 | Viewed by 8823

Vaccines are among the most effective public health interventions, significantly reducing morbidity and mortality from infectious diseases. Despite their proven efficacy, vaccine hesitancy has emerged as a pressing global challenge. This review examines the drivers, barriers, and interventions associated with vaccine hesitancy and [...] Read more.

Vaccines are among the most effective public health interventions, significantly reducing morbidity and mortality from infectious diseases. Despite their proven efficacy, vaccine hesitancy has emerged as a pressing global challenge. This review examines the drivers, barriers, and interventions associated with vaccine hesitancy and uptake, focusing on childhood vaccinations and the role of parents as primary decision-makers. Misinformation, safety concerns, and political decisions have contributed to declining vaccination rates, posing threats to public health. The article proposes targeted programs and policies to rebuild vaccine confidence, emphasizing the role of trusted messengers, health literacy, and structural reforms to reduce barriers. Recommendations highlight the importance of accurate information, open communication, and advocacy for school vaccine mandates. The conclusion stresses the urgent need to implement robust policies and community-based initiatives to ensure widespread immunization and safeguard population health. Full article

(This article belongs to the Special Issue Impact of Immunization Safety Monitoring on Vaccine Coverage)

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18 pages, 523 KB

Open AccessEditor’s ChoiceSystematic Review

Strategies to Increase Vaccinations in Adult Cancer Patients: A Systematic Review

by Giuseppina Lo Moro, Federica Golzio, Sara Claudia Calabrese, Giacomo Scaioli, Alessandro Basile, Roberta Siliquini and Fabrizio Bert

Vaccines 2025, 13(9), 964; https://doi.org/10.3390/vaccines13090964 - 11 Sep 2025

Cited by 4 | Viewed by 2360

Abstract

Background/Objectives: Although vaccinations are a priority for patients with cancer, achieving high coverage remains challenging. Evidence on effective strategies in oncology settings is still limited. This systematic review aimed to identify interventions to improve vaccination uptake or reduce hesitancy among cancer patients. Methods: [...] Read more.

Background/Objectives: Although vaccinations are a priority for patients with cancer, achieving high coverage remains challenging. Evidence on effective strategies in oncology settings is still limited. This systematic review aimed to identify interventions to improve vaccination uptake or reduce hesitancy among cancer patients. Methods: A systematic search was conducted in PubMed, Embase, and Scopus, including studies published up to the end of 2023. The protocol was registered in PROSPERO (CRD42024511008). Results: Out of 10,927 non-duplicate records, 15 studies describing unique interventions were included. All studies were published between 2011 and 2022, primarily conducted in Europe/UK (40%) and in North America (40%). The most common study design was pre-post (60%), and 33.3% included a control group. Most interventions were multi-component (60%) and were classified into three main categories: educational materials/campaigns (46.7%), reminders (40%), and patient counselling (33.3%). Additional components included guideline development in two studies. Some studies also highlighted the importance of specific key figures, such as dedicated professionals, general practitioners, and pharmacists. Interventions mainly targeted patients (40%), with 33.3% addressing both healthcare professionals and patients and 26.7% professionals only. They most frequently concerned vaccinations against influenza and pneumococcal disease (26.7%), pneumococcal disease alone (26.7%), or Coronavirus Disease 2019 (COVID-19) (26.7%). Vaccination uptake was the primary outcome in 86.7% of studies, with 66.7% reporting significant improvements. Conclusions: This review identified a variety of strategies, with education, reminders, and counselling as key components. Multicomponent interventions and those involving both patients and providers were most promising. However, methodological limitations and limited generalizability highlighted the need for more rigorous research. Full article

(This article belongs to the Special Issue Virus Pandemics and Vaccinations)

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39 pages, 526 KB

Open AccessEditor’s ChoiceReview

Influenza Vaccines: Current Status, Adjuvant Strategies, and Efficacy

by Vijay Reddy Mokalla, Shirisha Gundarapu, Radhey S. Kaushik, Mrigendra Rajput and Hemachand Tummala

Vaccines 2025, 13(9), 962; https://doi.org/10.3390/vaccines13090962 - 11 Sep 2025

Cited by 17 | Viewed by 13227

Abstract

The influenza virus is one of the major global health concerns, causing significant morbidity and mortality in both humans and animals, with substantial impacts on public health. Vaccination remains the primary strategy for managing influenza virus infections; however, the virus undergoes frequent genetic [...] Read more.

The influenza virus is one of the major global health concerns, causing significant morbidity and mortality in both humans and animals, with substantial impacts on public health. Vaccination remains the primary strategy for managing influenza virus infections; however, the virus undergoes frequent genetic changes through antigenic drift and shift. These mutations lead to new seasonal strains that evade pre-existing immunity. These mutations can potentially result in virulent strains that could trigger future pandemics. Therefore, developing a vaccine capable of providing robust protection despite these genetic changes is essential. Vaccine adjuvants are essential for boosting and directing the immune system’s response, broadening the spectrum of protection, and reducing the amount of antigen required to achieve protection, which is particularly valuable in the face of rapidly evolving strains and during pandemics. Recent advances in adjuvant design and formulation strategies have demonstrated promising improvements in both the overall potency and durability of influenza vaccines, importantly, significant reductions in losses due to influenza infection. This review highlights the current status of different types of influenza virus vaccines, their benefits, and challenges. Further, the review focuses on the role of adjuvants, discussing their advantages, limitations, and methodological approaches, while also considering their potential contribution in developing a universal flu vaccine intended to provide extensive and lasting protection. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

21 pages, 2497 KB

Open AccessEditor’s ChoiceReview

Emerging Therapeutic Strategies for Lung Cancer: The Role of Immunotherapy and HPV-Targeted Cancer Vaccines

by Krupa Bhaliya, Muneera Anwer and Ming Q. Wei

Vaccines 2025, 13(9), 957; https://doi.org/10.3390/vaccines13090957 - 8 Sep 2025

Cited by 4 | Viewed by 2928

Abstract

Background/Objectives: Lung cancer remains the leading cause of cancer-related deaths globally, with non-small-cell lung cancer (NSCLC) accounting for most cases. Although advances in targeted therapies and immunotherapy have improved outcomes, long-term survival remains limited. This review aims to explore current immunotherapeutic strategies, [...] Read more.

Background/Objectives: Lung cancer remains the leading cause of cancer-related deaths globally, with non-small-cell lung cancer (NSCLC) accounting for most cases. Although advances in targeted therapies and immunotherapy have improved outcomes, long-term survival remains limited. This review aims to explore current immunotherapeutic strategies, the evolving role of therapeutic cancer vaccines, and the emerging potential of human papillomavirus-targeted interventions in lung cancer, particularly among non-smoker populations. Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and Web of Science databases to identify relevant articles published between 2015 and 2024. Studies focusing on immune checkpoint inhibitors, vaccine platforms, HPV-associated lung cancer, tumor microenvironment modulation, and novel delivery systems such as bacterial ghosts were included. Relevant clinical trials and preclinical studies were critically evaluated and synthesized. Results: Immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4 have demonstrated clinical efficacy in NSCLC, yet their effectiveness is often limited by resistance mechanisms and lack of robust predictive biomarkers. Cancer vaccines, including peptide-based, mRNA, DNA, dendritic cell, and bacterial ghost platforms are emerging as complementary strategies to enhance antitumor immunity. Moreover, accumulating evidence suggests a potential association between high-risk HPV infection and lung cancer development, supporting the rationale for HPV-targeted vaccine strategies. Conclusions: Immunotherapy and therapeutic vaccination hold significant promise in reshaping lung cancer treatment. Advancements in vaccine design, delivery platforms like bacterial ghosts, and better understanding of HPV’s role in lung oncogenesis could support more effective, personalized immunotherapeutic approaches in the future. Full article

(This article belongs to the Special Issue Innovative Vaccines That Modulate the Immune System to Enhance Cancer Therapy)

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19 pages, 283 KB

Open AccessEditor’s ChoiceReview

Immunization Strategies in Pediatric Patients Receiving Hematopoietic Cell Transplantation (HCT) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Challenges and Insights from a Narrative Review

by Daniele Zama, Laura Pedretti, Gaia Capoferri, Roberta Forestiero, Marcello Lanari and Susanna Esposito

Vaccines 2025, 13(9), 932; https://doi.org/10.3390/vaccines13090932 - 1 Sep 2025

Cited by 3 | Viewed by 2882

Abstract

Background: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy have markedly improved survival in pediatric patients with hematological malignancies. However, these treatments cause profound immunosuppression, leading to significant susceptibility to vaccine-preventable diseases (VPDs), including invasive pneumococcal disease and measles. Timely [...] Read more.

Background: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy have markedly improved survival in pediatric patients with hematological malignancies. However, these treatments cause profound immunosuppression, leading to significant susceptibility to vaccine-preventable diseases (VPDs), including invasive pneumococcal disease and measles. Timely and tailored immunization strategies are crucial to mitigate infectious risks in this vulnerable population. Methods: We conducted a narrative review of the English-language literature from 2000 to 2024, including clinical guidelines, surveys, and original studies, to evaluate immune reconstitution and vaccination practices in pediatric patients undergoing HCT and CAR-T therapy. Literature searches in PubMed, Scopus, and Web of Science used disease-specific, therapy-specific, and pathogen-specific terms. Data synthesis focused on vaccine schedules, immune recovery markers, and adherence challenges. Results: Profound immune deficits post-HCT and CAR-T therapy compromise both innate and adaptive immunity, often necessitating revaccination. Key factors influencing vaccine responses include time since therapy, graft source, immunosuppressive treatments, and chronic graft-versus-host disease. Although inactivated vaccines are generally safe from three to six months post-HCT, live vaccines remain contraindicated until documented immune recovery. CAR-T therapy introduces unique challenges due to prolonged B-cell aplasia and hypogammaglobulinemia, leading to delayed or reduced vaccine responses. Despite established guidelines, real-world adherence to vaccination schedules remains suboptimal, driven by institutional, logistic, and patient-related barriers. Conclusions: Effective vaccination strategies are essential for reducing infectious morbidity in pediatric HCT and CAR-T recipients. Personalized vaccine schedules, immune monitoring, and multidisciplinary coordination are critical to bridging gaps between guidelines and practice, ultimately improving long-term outcomes for immunocompromised children. Full article

(This article belongs to the Special Issue Childhood Immunization and Public Health)

29 pages, 1172 KB

Open AccessEditor’s ChoiceReview

Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook

by Yiyang Zheng, Yusheng Pei, Chunyan Dong, Jinghui Liang, Tong Cai, Yuan Zhang, Dejiang Tan, Junzhi Wang and Qing He

Vaccines 2025, 13(8), 880; https://doi.org/10.3390/vaccines13080880 - 20 Aug 2025

Cited by 6 | Viewed by 5656

Abstract

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval [...] Read more.

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies. Full article

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25 pages, 376 KB

Open AccessEditor’s ChoiceReview

Research Progress of Universal Influenza Vaccine

by Liangliang Wang, Qian Xie, Pengju Yu, Jie Zhang, Chenchen He, Weijin Huang, Youchun Wang and Chenyan Zhao

Vaccines 2025, 13(8), 863; https://doi.org/10.3390/vaccines13080863 - 15 Aug 2025

Cited by 7 | Viewed by 9025

Abstract

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza [...] Read more.

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza vaccines and their advantages and disadvantages in universal vaccine design. We also summarize the common design strategies for universal influenza vaccines, which mainly include the immunofocusing strategy, multi-target combination strategy, T-cell strategy, computationally optimized broadly cross-reactive antigenic strategy (COBRA), and artificial intelligence strategy. In addition, we also sort out the latest research progress of universal influenza vaccines under different technological routes. This will help researchers better grasp the latest developments of universal influenza vaccines. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

23 pages, 1964 KB

Open AccessEditor’s ChoiceReview

Freeze-Drying of mRNA-LNPs Vaccines: A Review

by MD Faizul Hussain Khan, Floriane Baudin, Ayyappasamy Sudalaiyadum Perumal and Amine A. Kamen

Vaccines 2025, 13(8), 853; https://doi.org/10.3390/vaccines13080853 - 12 Aug 2025

Cited by 14 | Viewed by 7017

Abstract

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA [...] Read more.

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA vaccines by converting them into a stable dry powder. The purpose of this review is to provide an overview of the current knowledge on the progress of freeze-drying techniques for mRNA vaccines, with emphasis on the associated challenges. This review highlights the factors influencing the stability of freeze-dried mRNA vaccines and provides a comprehensive overview of the formulation components, including excipients, buffers, and surfactants, as well as the process parameters and storage conditions that aim to improve stability and shelf-life. By providing these insights, this review supports the advancement of more robust, scalable, and efficient lyophilization protocols, ultimately addressing the stability limitations of mRNA vaccines and enhancing their global accessibility. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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18 pages, 388 KB

Open AccessEditor’s ChoiceReview

A Narrative Review on How Timing Matters: Circadian and Sleep Influences on Influenza Vaccine Induced Immunity

by Achilleas Livieratos, Jamie M. Zeitzer and Sotirios Tsiodras

Vaccines 2025, 13(8), 845; https://doi.org/10.3390/vaccines13080845 - 8 Aug 2025

Cited by 4 | Viewed by 5307

Abstract

We aimed to synthesize and critically evaluate human studies on the impact of circadian and sleep factors on influenza vaccine-induced immune responses. A comprehensive literature review was conducted, and of the 1260 studies identified, 13 met the inclusion criteria for evaluating vaccination timing, [...] Read more.

We aimed to synthesize and critically evaluate human studies on the impact of circadian and sleep factors on influenza vaccine-induced immune responses. A comprehensive literature review was conducted, and of the 1260 studies identified, 13 met the inclusion criteria for evaluating vaccination timing, circadian misalignment, and sleep parameters in relation to influenza vaccine-induced immune responses in human populations. Most studies assessed humoral immune responses, primarily antibody titers. Morning vaccination (typically between 9:00 and 11:00 AM) was associated with higher antibody titers compared to afternoon vaccination, particularly for the A/H1N1 strain in adults aged ≥ 65 years. Short sleep duration—especially in the two nights preceding vaccination—was associated with reduced antibody levels, while acute sleep deprivation the night after vaccination transiently reduced antibody levels in males. Sleep fragmentation and excessive daytime sleepiness were linked to increased vulnerability to breakthrough infections. Evidence on circadian misalignment from shift work was mixed. Clinical outcomes were reported in one large trial, where morning vaccination correlated with fewer respiratory hospitalizations. Current evidence supports a potential role for circadian timing and sleep duration in enhancing vaccine-induced antibody responses, particularly in older adults and individuals with sleep or circadian disruption. However, inconsistencies, modest effect sizes, and methodological limitations preclude broad recommendations. Future studies should incorporate direct measures of circadian phase, stratify by chronotype and population (e.g., shift workers), and evaluate both immunologic and clinical outcomes to inform targeted chrono-immunization strategies. Full article

(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)

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12 pages, 2630 KB

Open AccessEditor’s ChoiceArticle

Evaluating the Relationship Between the Introduction of the Acellular Pertussis Vaccine and Whooping Cough Resurgence in the United States

by Jeegan Parikh, Ismael Hoare and Ricardo Izurieta

Vaccines 2025, 13(8), 841; https://doi.org/10.3390/vaccines13080841 - 7 Aug 2025

Cited by 5 | Viewed by 5414

Abstract

Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United [...] Read more.

Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United States and the change in the type of pertussis vaccines. Methods: Pertussis cases from 1922 to 2024 were obtained from the CDC’s national notifiable disease surveillance system, and vaccination coverage was obtained from the WHO. A trend analysis and Pearson’s correlation test were conducted between the incidence of cases and the coverage of the third and fourth doses of the pertussis vaccine. An ANOVA test and multivariable linear regression were performed to assess the association between the type of vaccine and the number of pertussis cases. Results: The number of cases increased from 4083 in 1992 to 35,435 in 2024, with cyclical outbreaks in 2010, 2012–2014, and 2024. The third and fourth doses of pertussis vaccine coverage had mild and moderate correlations with the number of pertussis cases. The vaccine type had a significant association with the number of pertussis cases and stayed significant after adjusting for vaccination coverage. Conclusions: The switch in pertussis vaccine has impacted the epidemiology of pertussis outbreaks in the United States. A combination of factors, such as different types of immune response to vaccines, waning of immunity, and selection of non-vaccine bacterial strains, may explain the observed results. Further research on newer, improved vaccinations or alternative schedules in children needs to be conducted to address the resurgence of pertussis in this study. Full article

(This article belongs to the Special Issue Vaccination, Public Health and Epidemiology)

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32 pages, 2027 KB

Open AccessEditor’s ChoiceReview

Harnessing the Loop: The Perspective of Circular RNA in Modern Therapeutics

by Yang-Yang Zhao, Fu-Ming Zhu, Yong-Juan Zhang and Huanhuan Y. Wei

Vaccines 2025, 13(8), 821; https://doi.org/10.3390/vaccines13080821 - 31 Jul 2025

Cited by 7 | Viewed by 6702

Abstract

Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and [...] Read more.

Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and modular delivery platforms are accelerating clinical translation. In this review, we synthesize recent advances in circRNA therapeutics, with a focused analysis of their stability and immunogenic properties in vaccine and drug development. Notably, key synthesis strategies, delivery platforms, and AI-driven optimization methods enabling scalable production are discussed. Moreover, we summarize preclinical and emerging clinical studies that underscore the potential of circRNA in vaccine development and protein replacement therapies. As both a promising expression vehicle and programmable regulatory molecule, circRNA represents a versatile platform poised to advance next-generation biologics and precision medicine. Full article

(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)

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23 pages, 1372 KB

Open AccessEditor’s ChoiceArticle

Immunization with Complete Freund’s Adjuvant Reveals Trained Immunity-like Features in A/J Mice

by Kiruthiga Mone, Shraddha Singh, Fatema Abdullatif, Meghna Sur, Mahima T. Rasquinha, Javier Seravalli, Denise K. Zinniel, Indranil Mukhopadhyay, Raul G. Barletta, Teklab Gebregiworgis and Jay Reddy

Vaccines 2025, 13(7), 768; https://doi.org/10.3390/vaccines13070768 - 21 Jul 2025

Cited by 4 | Viewed by 3429

Abstract

Background/Objectives: Freund’s adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund’s adjuvant (CFA) involve the mechanisms of trained immunity (TI). Methods: We examined bone marrow cells (BMCs) [...] Read more.

Background/Objectives: Freund’s adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund’s adjuvant (CFA) involve the mechanisms of trained immunity (TI). Methods: We examined bone marrow cells (BMCs) isolated from CFA-immunized A/J mice to address this question. Incomplete Freund’s adjuvant (IFA) and Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin (BCG) served as negative and positive controls, respectively. We evaluated cytokine profiles, metabolic, and epigenetic changes. Results: First, BMCs from all groups except saline showed varied levels of IL-1β, IL-6, and TNF-α. But expression of CCL5 and CXCL10 was significantly elevated only in the CFA and BCG groups. Transcriptionally, significant elevations were noted for TNF-α and IL-1β in the CFA and BCG groups, whereas CXCL10, IL-6, and IL-10 were upregulated in the CFA and BCG groups, respectively. Second, while BMCs from the BCG group expressed the markers of both the M1 and M2 macrophages, no clear trends were noted in the CFA and IFA groups. Third, cell lysates from the CFA group revealed metabolic reprogramming in the BMCs. Specifically, we observed an increased level of lactate, indicative of aerobic glycolysis, which is implicated in TI, and this was also detected in the IFA group. Fourth, epigenetic analysis revealed histone enrichment in the promoter region of TNF-α, in the CFA group, but to a lesser degree than the BCG group. However, no epigenetic changes were observed in the IFA group. Conclusions: Our data provide new insights into the mechanisms of Freund’s adjuvants and the immunomodulatory effects of CFA could involve the features of TI. Full article

(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)

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67 pages, 4242 KB

Open AccessEditor’s ChoiceReview

Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives

by Ayesha Zahid, Hazrat Ismail, Jennifer C. Wilson and I. Darren Grice

Vaccines 2025, 13(7), 767; https://doi.org/10.3390/vaccines13070767 - 20 Jul 2025

Cited by 18 | Viewed by 9054

Abstract

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic [...] Read more.

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

(This article belongs to the Special Issue Bioengineering Strategies for Developing Vaccines)

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21 pages, 492 KB

Open AccessEditor’s ChoiceReview

Research Progress on Varicella-Zoster Virus Vaccines

by Hongjing Liu, Lingyan Cui, Sibo Zhang, Hong Wang, Wenhui Xue, Hai Li, Yuyun Zhang, Lin Chen, Ying Gu, Tingting Li, Ningshao Xia and Shaowei Li

Vaccines 2025, 13(7), 730; https://doi.org/10.3390/vaccines13070730 - 4 Jul 2025

Cited by 7 | Viewed by 7026

Abstract

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has [...] Read more.

Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has substantially reduced the global incidence of these diseases. However, live attenuated vaccines raise concerns regarding safety and immunogenicity, especially in immunocompromised populations, while recombinant subunit vaccines, such as Shingrix, exhibit high efficacy but are associated with side effects and adjuvant limitations. Recent advancements in vaccine technology, including mRNA vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines, offer promising alternatives with improved safety profiles and durable immunity. This review synthesizes current knowledge on VZV vaccine mechanisms, clinical applications, and immunization strategies, while also examining future directions in vaccine development. The findings underscore the pivotal role of VZV vaccines in disease prevention and highlight the need for continued research to enhance their public health impact. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

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12 pages, 631 KB

Open AccessEditor’s ChoiceReview

Challenges and Limitations of Current RSV Prevention Strategies in Infants and Young Children: A Narrative Review

by Nicola Principi, Serafina Perrone and Susanna Esposito

Vaccines 2025, 13(7), 717; https://doi.org/10.3390/vaccines13070717 - 1 Jul 2025

Cited by 12 | Viewed by 5685

Abstract

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal [...] Read more.

Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal immunization. While these interventions have improved early protection, several limitations hinder their broader impact and long-term effectiveness. Methods: This narrative review synthesizes evidence from clinical trials, observational studies, and regulatory reports to evaluate the main limitations of nirsevimab and maternal RSV vaccination. Literature searches were conducted in major databases, focusing on efficacy, safety, immunogenicity, implementation, and population-specific challenges. Results: Both nirsevimab and maternal vaccination provide strong protection during the first six months of life, but their effectiveness wanes thereafter. This is concerning as nearly half of RSV-related deaths occur in children over six months old. Maternal vaccine efficacy is uncertain in very-preterm infants, and safety concerns persist, including potential associations with preterm birth, Guillain–Barré syndrome, and hypertensive disorders. Real-world data from low-income countries are lacking, limiting generalizability. Additionally, the risk of vaccine-associated enhanced disease (VAED), although unconfirmed, has delayed pediatric vaccine development. Emerging monoclonal antibodies and live-attenuated vaccines are under investigation to extend protection beyond infancy. Conclusions: Despite substantial progress, current RSV prevention strategies leave critical gaps, particularly for older infants and underserved populations. There is a pressing need for next-generation vaccines, enhanced pharmacovigilance, and equitable global implementation to ensure sustained and inclusive RSV protection. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)

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21 pages, 323 KB

Open AccessEditor’s ChoiceReview

Progress and Recent Developments in HIV Vaccine Research

by Iris Shim, Lily Rogowski and Vishwanath Venketaraman

Vaccines 2025, 13(7), 690; https://doi.org/10.3390/vaccines13070690 - 26 Jun 2025

Cited by 11 | Viewed by 15681

Abstract

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of [...] Read more.

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article

(This article belongs to the Special Issue Advances in HIV Vaccine Development, 2nd Edition)

15 pages, 2783 KB

Open AccessEditor’s ChoiceArticle

Childhood Immunization Coverage Before, During and After the COVID-19 Pandemic in Italy

by Flavia Pennisi, Andrea Silenzi, Alessia Mammone, Andrea Siddu, Anna Odone, Michela Sabbatucci, Riccardo Orioli, Anna Carole D’Amelio, Francesco Maraglino, Giovanni Rezza and Carlo Signorelli

Vaccines 2025, 13(7), 683; https://doi.org/10.3390/vaccines13070683 - 25 Jun 2025

Cited by 5 | Viewed by 3673

Abstract

Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate [...] Read more.

Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate national and regional trends in vaccine coverage across three phases: post-mandate (2015–2016 vs. 2017–2019), pandemic (2017–2019 vs. 2020–2021), and post-pandemic recovery (2020–2021 vs. 2022–2023). Methods: National and regional administrative data on vaccination coverage at 24 months of age were obtained from the Italian Ministry of Health. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs), and absolute changes in coverage (Δ) were calculated across defined periods. Pearson correlation coefficients were used to assess associations between baseline coverage and subsequent changes. Results: After the 2017 mandate, coverage increased significantly for varicella (APC = +28.6%), MenB (+22.6%), and measles (+3.4%). Regionally, varicella coverage rose by up to +58.4% in Emilia-Romagna and measles by +11.1% in Campania. During the pandemic, coverage declined for polio (−2.4% in the South) and measles (−6.2% in Abruzzo), while MenB increased in regions with lower initial uptake (r = −0.918, p < 0.001). Post-pandemic, coverage rebounded, with varicella improving by +20.1% in central regions and measles by +13.9% in Abruzzo. A strong inverse correlation between baseline coverage and improvement was observed for varicella across all periods (r from −0.877 to −0.915). Conclusions: Mandatory vaccination policies led to substantial coverage improvements, and despite the disruption caused by the pandemic, recovery trends were observed for most vaccines. The consistent association between low baseline coverage and stronger gains highlights the resilience of the system, but also the ongoing need for regionally tailored strategies to reduce geographic disparities and ensure equitable immunization across Italy. Full article

(This article belongs to the Section Vaccines and Public Health)

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15 pages, 421 KB

Open AccessEditor’s ChoiceReview

VITT Pathophysiology: An Update

by Eleonora Petito and Paolo Gresele

Vaccines 2025, 13(6), 650; https://doi.org/10.3390/vaccines13060650 - 17 Jun 2025

Cited by 3 | Viewed by 3146

Abstract

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation [...] Read more.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation in the presence of PF4. In addition to this immune-based pathomechanism, random splicing events of the Adv-vector DNA encoding for SARS-CoV-2 spike protein resulting in the secretion of soluble spike variants have been postulated as a possible pathophysiological mechanism. More recently, some novel clinical-pathological anti-PF4-associated entities also characterized by thrombosis, thrombocytopenia, and VITT-like antibodies but independent from heparin or AdV-vaccine administration have been identified. To date, these VITT-like disorders have been reported following the administration of vaccines different from anti-SARS-CoV-2 AdV-vaccines, like human papillomavirus (HPV) and mRNA-based COVID-19 vaccines, following a bacterial or viral respiratory infection, and in patients with a monoclonal gammopathy of undetermined significance. The purpose of this review is to provide an update on the knowledge on VITT pathogenesis, focusing on recent findings on anti-PF4 antibodies, on a possible genetic predisposition to VITT, on VITT-antibody intracellular activated pathways, on lipid metabolism alterations, and on new VITT-like disorders. Full article

(This article belongs to the Special Issue Vaccine-Induced Immune Thrombotic Thrombocytopenia)

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17 pages, 312 KB

Open AccessEditor’s ChoiceReview

Human Alpha Herpesviruses Infections (HSV1, HSV2, and VZV), Alzheimer’s Disease, and the Potential Benefits of Targeted Treatment or Vaccination—A Virological Perspective

by Peter A. C. Maple and Akram A. Hosseini

Vaccines 2025, 13(6), 572; https://doi.org/10.3390/vaccines13060572 - 27 May 2025

Cited by 5 | Viewed by 6975

Abstract

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) [...] Read more.

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article

(This article belongs to the Special Issue Varicella and Zoster Vaccination)

16 pages, 7103 KB

Open AccessEditor’s ChoiceArticle

Adjuvanted RNA Origami—A Tunable Peptide Assembly Platform for Constructing Cancer Nanovaccines

by Theresa Yip, Xinyi Tu, Xiaodong Qi, Hao Yan and Yung Chang

Vaccines 2025, 13(6), 560; https://doi.org/10.3390/vaccines13060560 - 25 May 2025

Cited by 4 | Viewed by 2666

Abstract

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as [...] Read more.

Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG. Methods: Here, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity. Results: Although the vaccines with a high number of peptides, i.e., 100–200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8⁺ T cell responses against engrafted tumor cells, probably owing to an induction of early T cell exhaustion. Interestingly, the same vaccine format with a low number of peptides, i.e., 10–15 peptides/RNA-OG, enhanced CD8⁺ T cell responses without provoking T cell exhaustion in tumor-bearing mice, leading to strong protective anti-tumor immunity. In comparison, the covalently assembled RNA-OG-peptide vaccine, having a similarly low peptide dosage, offered the highest therapeutic efficacy. Thus, our RNA-OG nanostructure provides a simple and tunable platform for peptide loading to optimize vaccine efficacy. Conclusions: Our findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy. Full article

(This article belongs to the Special Issue Novel Immunotherapies, Cell Therapies and Cancer Vaccines)

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22 pages, 5356 KB

Open AccessEditor’s ChoiceArticle

Mucosal and Serum Neutralization Immune Responses Elicited by COVID-19 mRNA Vaccination in Vaccinated and Breakthrough-Infection Individuals: A Longitudinal Study from Louisville Cohort

by Lalit Batra, Divyasha Saxena, Triparna Poddar, Maryam Zahin, Alok Amraotkar, Megan M. Bezold, Kathleen T. Kitterman, Kailyn A. Deitz, Amanda B. Lasnik, Rachel J. Keith, Aruni Bhatnagar, Maiying Kong, Jon D. Gabbard, William E. Severson and Kenneth E. Palmer

Vaccines 2025, 13(6), 559; https://doi.org/10.3390/vaccines13060559 - 24 May 2025

Cited by 4 | Viewed by 2280

Abstract

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the [...] Read more.

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development: 2nd Edition)

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20 pages, 986 KB

Open AccessEditor’s ChoiceReview

Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review

by Justin Tang, Md Al Amin and Jian L. Campian

Vaccines 2025, 13(5), 524; https://doi.org/10.3390/vaccines13050524 - 15 May 2025

Cited by 24 | Viewed by 11644

Abstract

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often [...] Read more.

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article

(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)

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24 pages, 592 KB

Open AccessEditor’s ChoiceReview

Addressing the Underestimated Burden of RSV in Older Adults in Europe: Epidemiology, Surveillance Gaps, and Public Health Implications

by Floriana D’Ambrosio, Marta Lomazzi, Michael Moore, Ada Maida, Roberto Ricciardi, Ludovica Munno, Monia Lettieri, Elisabetta De Vito, Walter Ricciardi and Giovanna Elisa Calabrò

Vaccines 2025, 13(5), 510; https://doi.org/10.3390/vaccines13050510 - 12 May 2025

Cited by 11 | Viewed by 6933

Abstract

Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating [...] Read more.

Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating the burden in older and high-risk adults. This review aims to synthesize current evidence on the epidemiological and clinical impact of RSV in older adults in Europe, assess existing surveillance strategies, and identify gaps to guide targeted public health responses. Methods: A two-phase research strategy was adopted. First, a comprehensive review of studies published between 2015–2025 was conducted via PubMed, focusing on the RSV burden in high-risk and elderly populations in Europe. Second, a structured web screening was performed to assess the status of existing RSV surveillance systems, focusing on eight selected European countries. Results: The review reported RSV prevalence rates ranging from 1% to 64.7% among older adults, with a high prevalence of comorbidities that exacerbate disease severity. Hospitalization rates varied between 12.6–55.9%, while mortality ranged from 2.15% to 13%, reaching up to 36% in intensive care settings. Surveillance systems for adult RSV infections across Europe remain limited and fragmented, with only 37.5% (3/8) of analyzed countries having dedicated surveillance for adults. Conclusions: RSV represents a substantial and underrecognized threat to older adults, with significant clinical and healthcare implications. Strengthening surveillance, standardizing data collection, and ensuring equitable access to newly available preventive measures are urgent priorities to reduce the disease burden, protect vulnerable populations, and support resilient health systems against future health challenges. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)

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13 pages, 231 KB

Open AccessEditor’s ChoiceReview

Dengue Vaccine Development and Deployment into Routine Immunization

by Annelies Wilder-Smith, Thomas Cherian and Joachim Hombach

Vaccines 2025, 13(5), 483; https://doi.org/10.3390/vaccines13050483 - 29 Apr 2025

Cited by 12 | Viewed by 8207

Abstract

Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly [...] Read more.

Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly in high-burden regions. TAK-003, a tetravalent live-attenuated vaccine, has demonstrated 61% efficacy against virologically confirmed dengue and 84% efficacy against hospitalizations in endemic settings. However, concerns remain about vaccine-enhanced disease, particularly among seronegative individuals exposed to DENV3 and DENV4. WHO recommends targeted introduction in high-transmission settings without pre-vaccination screening, while ongoing post-introduction studies will further clarify long-term safety and efficacy. Effective vaccine rollout requires a multi-pronged approach, including school-based immunization, integration with adolescent health services, and strong community engagement. Decision-making for vaccine introduction should be guided by National Immunization Technical Advisory Groups (NITAGs), local epidemiological data, and cost-effectiveness assessments. While future vaccines, including mRNA and virus-like particle candidates, are under development, optimizing the use of currently available vaccines is crucial to reducing dengue’s public health impact. Given the continued rise in cases, immediate action—combining vaccination with vector control—is essential to prevent further morbidity and mortality. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

19 pages, 3320 KB

Open AccessEditor’s ChoiceArticle

Generation of Chimeric African Swine Fever Viruses Through In Vitro and In Vivo Intergenotypic Gene Complementation

by Tomoya Kitamura, Kentaro Masujin, Mitsutaka Ikezawa, Aruna Ambagala and Takehiro Kokuho

Vaccines 2025, 13(5), 462; https://doi.org/10.3390/vaccines13050462 - 25 Apr 2025

Cited by 10 | Viewed by 2733

Abstract

Background/Objectives: African swine fever (ASF), a fatal febrile hemorrhagic disease in domestic pigs and Eurasian wild boars, is caused by ASF virus (ASFV). ASF continues to spread across the globe, causing a significant impact on the world’s pig industry. Recently, highly virulent [...] Read more.

Background/Objectives: African swine fever (ASF), a fatal febrile hemorrhagic disease in domestic pigs and Eurasian wild boars, is caused by ASF virus (ASFV). ASF continues to spread across the globe, causing a significant impact on the world’s pig industry. Recently, highly virulent chimeric ASFV (chASFV) strains with recombined genomes of the p72 genotype I and II viruses have been reported in China, Vietnam and Russia. Methods: In order to understand the propensity of ASFV genome for recombination, we attempted to experimentally generate chASFVs both in vitro and in vivo employing two distinct attenuated ASFV strains: OUR T88/3 (genotype I) and AQSΔB119L (genotype II). Results: When IPKM cells were co-infected with ASFV OUR T88/3 and AQSΔB119L strains, three genetically distinct chASFV emerged. When pigs were inoculated with the individual chASFV isolates, all pigs developed acute ASF. When four pigs were co-infected with ASFV OUR T88/3 and AQSΔB119L, all of them developed acute ASF and died or were euthanized. Three chASFV strains were successfully isolated from splenic homogenates from each pig. Conclusions: Our research indicates that genotype I and II chASFV with diverse genomes can be easily generated experimentally both in vitro and in vivo. Full article

(This article belongs to the Section Veterinary Vaccines)

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22 pages, 723 KB

Open AccessEditor’s ChoiceReview

From Antibodies to Immunity: Assessing Correlates of Flavivirus Protection and Cross-Reactivity

by Hannah E. Flores, Eduar Fernando Pinzon Burgos, Sigrid Camacho Ortega, Alonso Heredia and Joel V. Chua

Vaccines 2025, 13(5), 449; https://doi.org/10.3390/vaccines13050449 - 24 Apr 2025

Cited by 7 | Viewed by 4600

Abstract

Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), [...] Read more.

Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), which help indicate host immunity after vaccination. Current vaccines primarily focus on neutralizing antibodies (nAbs) against the viral envelope E protein, though emerging evidence suggests other potential targets may also be effective in disease prevention. Additionally, there is growing evidence of cross-protection between different flaviviruses when immunity to one virus is achieved, although this can be limited by antibody-dependent enhancement. This review examines the current understanding of flavivirus immunity, CoPs, and the potential for cross-protection in the context of existing vaccine strategies. Full article

(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)

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19 pages, 689 KB

Open AccessEditor’s ChoiceReview

Maternal Immunization: Current Evidence, Progress, and Challenges

by Veronica Santilli, Mayla Sgrulletti, Giorgio Costagliola, Alessandra Beni, Maria Felicia Mastrototaro, Davide Montin, Caterina Rizzo, Baldassarre Martire, Michele Miraglia del Giudice and Viviana Moschese

Vaccines 2025, 13(5), 450; https://doi.org/10.3390/vaccines13050450 - 24 Apr 2025

Cited by 12 | Viewed by 11014

Abstract

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations [...] Read more.

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases. Full article

(This article belongs to the Special Issue Vaccines for the Vulnerable Population)

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27 pages, 819 KB

Open AccessEditor’s ChoiceReview

HPV Vaccine Delivery Strategies to Reach Out-of-School Girls in Low- and Middle-Income Countries: A Narrative Review

by Erica N. Rosser, Megan D. Wysong, Joseph G. Rosen, Rupali J. Limaye and Soim Park

Vaccines 2025, 13(5), 433; https://doi.org/10.3390/vaccines13050433 - 22 Apr 2025

Cited by 7 | Viewed by 5571

Abstract

Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented [...] Read more.

Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented through school-based immunization platforms. Unfortunately, this strategy risks missing out-of-school (OOS) girls (i.e., girls not enrolled in formal schools). This narrative review maps the literature and synthesizes existing evidence on service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Methods: Using relevant databases, we conducted a narrative review of published, peer-reviewed literature to map and synthesize the existing evidence on effective service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Results: The 21 articles identified presented findings on strategies to reach OOS girls, with the most frequently cited strategies being facility-based and community outreach approaches. Authors also described community-based strategies used to identify and enumerate OOS girls, including peer tracing, church outreach initiatives, as well as partnerships with local groups (e.g., civil service organizations) and individuals (e.g., healthcare workers, teachers). The articles discussed barriers at the individual (e.g., lack of parental consent), facility/program delivery (e.g., lack of transportation for vaccines), and community (e.g., distance from homes to vaccination services) levels to HPV vaccine delivery, as well as solutions at the facility/program delivery (e.g., pilot programs) and community (e.g., multi-level partnerships) levels. Conclusions: Additional research is needed to evaluate implementation strategies targeting OOS girls with HPV vaccination. A better understanding of these strategies can provide valuable insights for HPV vaccine policymakers, healthcare providers, and program implementers. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)

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12 pages, 1557 KB

Open AccessEditor’s ChoiceArticle

Neutralizing Antibody Response to the AreXvy Respiratory Syncytial Virus Vaccine in Lung Transplant Recipients: Assessment Against Reference and Seasonal Strains

by Liran Levy, Dafna Yahav, Mark Benzimra, Yael Bezalel, Tomer Hoffman, Neta Shirin, Tomer Sinai, Menucha Jurkowicz, Ofir Deri, Noa Matalon, Milton Saute, Yaniv Lustig, Eyal Nachum, Michael Peled, Ital Nemet and Michal Mandelboim

Vaccines 2025, 13(4), 398; https://doi.org/10.3390/vaccines13040398 - 11 Apr 2025

Cited by 4 | Viewed by 2785

Abstract

Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy^® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity [...] Read more.

Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy^® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity in solid organ transplant recipients remain unclear. Methods: A single-center retrospective cohort study, including all LTx recipients who were vaccinated with Arexvy in February 2024. Baseline and follow-up serum samples (1, 3, and 6 months post-vaccination) were analyzed for antibody responses using a commercial RSV ELISA kit and micro-neutralization assays against historical reference RSV A/B ATCC strains and seasonal RSV strains. Adverse events were documented. Results: A total of 28 recipients received the vaccine. Twenty-one (75%) were male, and the median age was 62 years (interquartile range [IQR], 53–67). The median time from transplant was 486 days (IQR, 243–966). Vaccination elicited strong immunogenic responses, demonstrating a twofold increase in ELISA-determined antibody levels at one month post-vaccination, which were sustained for six months. At one month, 67% of recipients had antibody levels exceeding the cutoff threshold. Micro-neutralization assays showed a significant increase in neutralizing antibodies against all tested variants (RSV A/B ATCC and seasonal RSV A/B), with titers remaining at least twofold higher than pre-vaccination levels. No serious adverse events were observed. Conclusions: Our findings demonstrate a sustained antibody response to the Arexvy^® vaccine in a cohort of LTx recipients, with antibody titers sustained over six months. Further research is needed to assess the long-term durability of the immune response and the potential immunogenicity of this vaccine in LTx populations. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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17 pages, 267 KB

Open AccessEditor’s ChoiceReview

The Application of mRNA Technology for Vaccine Production—Current State of Knowledge

by Anna Paczkowska, Karolina Hoffmann, Agata Andrzejczak, Weronika Faustyna Pucek, Dorota Kopciuch, Wiesław Bryl, Elżbieta Nowakowska and Krzysztof Kus

Vaccines 2025, 13(4), 389; https://doi.org/10.3390/vaccines13040389 - 4 Apr 2025

Cited by 5 | Viewed by 6684

Abstract

Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability [...] Read more.

Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability to trigger an immune response), and solving the challenge of delivering mRNA into cells—all to achieve a therapeutic effect. The aim of this study was to review the scientific literature on the use of mRNA technology in the production of vaccines. Various methods of applying mRNA technology that could potentially be introduced into clinical practice in the future are described. A detailed analysis was conducted on the approved COVID-19 vaccines developed by Pfizer/BioNTech (New York, NY, USA) and Moderna (Kirkland, QC, Canada), as their introduction marked a groundbreaking moment in the advancement of mRNA technology. This study was based on the latest scientific literature from reputable publishers and medical databases such as PubMed and ClinicalTrials. In conclusion, mRNA technology is currently experiencing rapid development, significantly driven by the ongoing COVID-19 pandemic. The application of this technology holds great potential not only for vaccines against infectious diseases but also for cancer treatment. However, further research is necessary to facilitate its broader clinical implementation. Full article

(This article belongs to the Special Issue Vaccine Development and Global Health)

25 pages, 1446 KB

Open AccessEditor’s ChoiceReview

Exploring CD169⁺ Macrophages as Key Targets for Vaccination and Therapeutic Interventions

by Rianne G. Bouma, Aru Z. Wang and Joke M. M. den Haan

Vaccines 2025, 13(3), 330; https://doi.org/10.3390/vaccines13030330 - 20 Mar 2025

Cited by 8 | Viewed by 6072

Abstract

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages [...] Read more.

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169⁺ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169⁺ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169⁺ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169⁺ macrophages in several disease settings and the vaccination strategies currently under investigation. Full article

(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)

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27 pages, 2149 KB

Open AccessEditor’s ChoiceArticle

Inflammatory and Humoral Immune Responses to Commercial Autogenous Salmonella Bacterin Vaccines in Light-Brown Leghorn Pullets: Primary and Secondary Vaccine Responses

by Chrysta N. Beck, Jossie M. Santamaria and Gisela F. Erf

Vaccines 2025, 13(3), 311; https://doi.org/10.3390/vaccines13030311 - 13 Mar 2025

Cited by 6 | Viewed by 2080

Abstract

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial [...] Read more.

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4⁺ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article

(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)

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19 pages, 2598 KB

Open AccessEditor’s ChoiceArticle

Prime-Boost Vaccination Based on Nanospheres and MVA Encoding the Nucleoprotein of Crimean-Congo Hemorrhagic Fever Virus Elicits Broad Immune Responses

by Eva Calvo-Pinilla, Sandra Moreno, Natalia Barreiro-Piñeiro, Juana M. Sánchez-Puig, Rafael Blasco, José Martínez-Costas, Alejandro Brun and Gema Lorenzo

Vaccines 2025, 13(3), 291; https://doi.org/10.3390/vaccines13030291 - 10 Mar 2025

Cited by 2 | Viewed by 2627

Abstract

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized [...] Read more.

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized nowadays for this particular virus. As CCHF (Crimean–Congo hemorrhagic fever) is a serious threat to public health, there is an urgent need to investigate the development of safe and effective vaccination strategies further. Methods: In this work, we have employed two immunization platforms based on protein nanoparticles and a modified vaccinia Ankara (MVA) viral vector using the nucleoprotein (NP) as the target antigen. The humoral and cellular immune responses were characterized by ELISA, ICS, and cytokine measurement. Results: This work shows that a single dose of the vaccine candidates was not as immunogenic as the heterologous vaccination using nanoparticles and MVA. A prime with NP nanoparticles (NS-NP) and a boost with MVA-expressing NP were capable of triggering significant levels of humoral and cellular immune responses against CCHFV in mice. Conclusions: Our study shows that the NS-NP/MVA-NP vaccination strategy effectively elicits a robust humoral and cellular immune response in a mouse model, emphasizing its potential as a protective approach against CCHFV lineages. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

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14 pages, 1648 KB

Open AccessEditor’s ChoiceArticle

Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4

by Bettina Wagner, Christiane L. Schnabel and Alicia Rollins

Vaccines 2025, 13(3), 290; https://doi.org/10.3390/vaccines13030290 - 10 Mar 2025

Cited by 5 | Viewed by 1715

Abstract

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and [...] Read more.

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)

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19 pages, 2176 KB

Open AccessEditor’s ChoiceArticle

Evaluating the Immunogenicity of an Intranasal Microparticle Combination Vaccine for COVID-19 and Influenza

by Sharon Vijayanand, Smital Patil, Priyal Bagwe, Revanth Singh, Emmanuel Adediran and Martin J. D’Souza

Vaccines 2025, 13(3), 282; https://doi.org/10.3390/vaccines13030282 - 7 Mar 2025

Cited by 2 | Viewed by 2994

Abstract

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination [...] Read more.

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination rates. To address the burden of frequent painful injections, this manuscript explores the potential of non-invasive intranasal (IN) vaccine administration as an effective alternative to intramuscular (IM) shots. Further, as a proof-of-concept, an inactivated combination vaccine for COVID-19 and influenza was tested to eliminate the need for separate vaccinations. Methods: The methods involved encapsulating antigens and adjuvants in poly(lactic-co-glycolic acid) (PLGA) polymer matrices, achieving over 85% entrapment. The vaccine was evaluated in vitro for cytotoxicity and immunogenicity before being administered to 6–8-week-old Swiss Webster mice at weeks 0, 3, and 6. The mice were then assessed for antibody levels and cellular responses. Results: The intranasal microparticle (IN-MP) vaccine induced an innate immune response, autophagy, and were non-cytotoxic in vitro. In vivo, the vaccine led to high levels of virus-specific serum IgM, IgG, and IgA binding antibodies, as well as elevated IgG and IgA levels in the lung wash samples. The antibodies generated demonstrated neutralizing activity against the SARS-CoV-2 pseudovirus. Furthermore, the IN-MP vaccine prompted increased antigen-specific CD4⁺ and CD8⁺ T-cell responses in the vaccinated mice. Conclusions: The IN-MP combination vaccine produced immune responses comparable to or higher than the IM route, indicating its potential as an alternative to IM injections. Full article

(This article belongs to the Special Issue Innovating Vaccine Research in Mucosal Vaccines)

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20 pages, 3294 KB

Open AccessEditor’s ChoiceSystematic Review

Evaluating the Immunogenicity, Efficacy, and Effectiveness of Recombinant Zoster Vaccine for Global Public Health Policy

by Lucy R. Williams, Joachim Hombach and Melanie Marti

Vaccines 2025, 13(3), 250; https://doi.org/10.3390/vaccines13030250 - 27 Feb 2025

Cited by 8 | Viewed by 6522

Abstract

Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We [...] Read more.

Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We performed a rapid review of studies evaluating the immunogenicity, efficacy, and effectiveness of RZV for protection against HZ and associated complications. We searched PubMed for English-language studies published between 7 August 2012 and 30 September 2023. Included studies reported vaccine efficacy or effectiveness against HZ and HZ-associated complications. Immunogenicity studies were included if they contributed to the understanding of RZV protection over time and/or co-administration with other vaccines. HZ outcomes were stratified by socio-demographic and clinical variables. Results: From 405 identified publications, 33 were eligible for the study. Most studies were conducted in the US (N = 12), across North America (N = 10), and Europe (N = 5), or across multiple locations across North America, Latin America, and Asia–Australia (N = 6). Vaccine efficacy against HZ in immunocompetent populations ranged between 90% and 97%, while effectiveness ranged between 71% and 86%. Protection stayed above 70% for at least 10 years, with no significant differences by age or ethnicity. Conclusions: RZV is effective in reducing the risk of HZ and its associated complications. Protection is long-lasting and the vaccine is suitable for older and immunocompromised populations. However, the decision to incorporate the vaccine into national policies depends on additional factors (e.g., cost-effectiveness), which may be difficult to characterize without an understanding of the global disease burden. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

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14 pages, 3979 KB

Open AccessEditor’s ChoiceArticle

Pre-Existing Anti-Vector Immunity to Adenovirus-Inspired VLP Vaccines Shows an Adjuvant-Dependent Antagonism

by Salomé Gallet, Dalil Hannani, Sebastian Dergan-Dylon, Emilie Vassal-Stermann, Isabelle Bally, Christopher Chevillard, Daphna Fenel, Olivier Epaulard, Pascal Poignard and Pascal Fender

Vaccines 2025, 13(3), 238; https://doi.org/10.3390/vaccines13030238 - 25 Feb 2025

Cited by 1 | Viewed by 3179

Abstract

Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived [...] Read more.

Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived from human-infecting viruses, preexisting immunity may influence the immune response they elicit, warranting further investigation. Methods: We have developed a 60-mer VLP derived from human adenovirus type 3, a common pathogen. We investigated the impact of pre-existing adenovirus immunity on the immunization outcome against the linear S14P5 epitope of SARS-CoV-2, which was engineered into the particle (Ad-VLP-S14P5). To this end, antibody responses to S14P5 were evaluated following immunization with Ad-VLP-S14P5 in either naive or vector-primed mice. Results: Mice with pre-existing anti-vector immunity exhibited significantly greater anti-S14P5 antibody responses compared to vector-naive animals, demonstrating a beneficial impact of prior anti-adenovirus responses. However, the addition of an oil-in-water adjuvant for the immunizations abolished this positive impact, even leading to a deleterious effect of the pre-existing anti-vector immunity. Conclusions: The data suggest that the immune status against immunizing VLPs must be taken into consideration when designing immunization protocols. Importantly, the effects of prior immunity may vary depending on the nature of the protocol, including factors such as adjuvant use. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles: The 3rd Edition)

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31 pages, 1245 KB

Open AccessEditor’s ChoiceReview

Advances and Challenges in Aeromonas hydrophila Vaccine Development: Immunological Insights and Future Perspectives

by Kavi R. Miryala and Banikalyan Swain

Vaccines 2025, 13(2), 202; https://doi.org/10.3390/vaccines13020202 - 18 Feb 2025

Cited by 30 | Viewed by 6568

Abstract

Aeromonas hydrophila presents a significant threat to global aquaculture due to its ability to infect freshwater and marine fish species, leading to substantial economic losses. Effective mitigation methods are essential to address these challenges. Vaccination has emerged as a promising strategy to reduce [...] Read more.

Aeromonas hydrophila presents a significant threat to global aquaculture due to its ability to infect freshwater and marine fish species, leading to substantial economic losses. Effective mitigation methods are essential to address these challenges. Vaccination has emerged as a promising strategy to reduce A. hydrophila infections; however, it faces several obstacles, including variability in immune responses, pathogen diversity, and environmental factors affecting vaccine efficacy. To enhance vaccine performance, researchers focus on adjuvants to boost immune responses and develop multivalent vaccines targeting multiple A. hydrophila strains. Tailoring vaccines to specific environmental conditions and optimizing vaccination schedules can further address the challenges posed by pathogen diversity and variable immune responses. This review provides an in-depth analysis of the immunological hurdles associated with A. hydrophila vaccine development. Current vaccine types—live attenuated, inactivated, subunit, recombinant, and DNA—exhibit diverse mechanisms for stimulating innate and adaptive immunity, with varying levels of success. Key focus areas include the potential of advanced adjuvants and nanoparticle delivery systems to overcome existing barriers. The review also highlights the importance of understanding host–pathogen interactions in guiding the development of more targeted and effective immune responses in fish. Complementary approaches, such as immunostimulants, probiotics, and plant-based extracts, are explored as adjuncts to vaccination in aquaculture health management. Despite notable progress, challenges remain in translating laboratory innovations into scalable, cost-effective solutions for aquaculture. Future directions emphasize the integration of advanced genomic and proteomic tools to identify novel antigen candidates and the need for industry-wide collaborations to standardize vaccine production and delivery. Addressing these challenges can unlock the potential of innovative vaccine technologies to safeguard fish health and promote sustainable aquaculture practices globally. Full article

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29 pages, 2354 KB

Open AccessEditor’s ChoiceReview

Molecular Farming for Immunization: Current Advances and Future Prospects in Plant-Produced Vaccines

by Dang-Khoa Vo and Kieu The Loan Trinh

Vaccines 2025, 13(2), 191; https://doi.org/10.3390/vaccines13020191 - 15 Feb 2025

Cited by 22 | Viewed by 14423

Abstract

Using plants as bioreactors, molecular farming has emerged as a versatile and sustainable platform for producing recombinant vaccines, therapeutic proteins, industrial enzymes, and nutraceuticals. This innovative approach leverages the unique advantages of plants, including scalability, cost-effectiveness, and reduced risk of contamination with human [...] Read more.

Using plants as bioreactors, molecular farming has emerged as a versatile and sustainable platform for producing recombinant vaccines, therapeutic proteins, industrial enzymes, and nutraceuticals. This innovative approach leverages the unique advantages of plants, including scalability, cost-effectiveness, and reduced risk of contamination with human pathogens. Recent advancements in gene editing, transient expression systems, and nanoparticle-based delivery technologies have significantly enhanced the efficiency and versatility of plant-based systems. Particularly in vaccine development, molecular farming has demonstrated its potential with notable successes such as Medicago’s Covifenz for COVID-19, illustrating the capacity of plant-based platforms to address global health emergencies rapidly. Furthermore, edible vaccines have opened new avenues in the delivery of vaccines, mainly in settings with low resources where the cold chain used for conventional logistics is a challenge. However, optimization of protein yield and stability, the complexity of purification processes, and regulatory hurdles are some of the challenges that still remain. This review discusses the current status of vaccine development using plant-based expression systems, operational mechanisms for plant expression platforms, major applications in the prevention of infectious diseases, and new developments, such as nanoparticle-mediated delivery and cancer vaccines. The discussion will also touch on ethical considerations, the regulatory framework, and future trends with respect to the transformative capacity of plant-derived vaccines in ensuring greater global accessibility and cost-effectiveness of the vaccination. This field holds great promise for the infectious disease area and, indeed, for applications in personalized medicine and biopharmaceuticals in the near future. Full article

(This article belongs to the Special Issue Production of Plant-Based Vaccines and Therapeutics)

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28 pages, 798 KB

Open AccessEditor’s ChoiceReview

Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

by Alex C. Boomgarden and Chitra Upadhyay

Vaccines 2025, 13(2), 148; https://doi.org/10.3390/vaccines13020148 - 31 Jan 2025

Cited by 21 | Viewed by 26397

Abstract

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability [...] Read more.

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines and mRNA technology to induce broadly neutralizing antibodies, have shown promise. However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. Ongoing research emphasizes the necessity of a multifaceted strategy to overcome these obstacles and achieve a breakthrough in HIV-1 vaccine development. This review summarizes current approaches utilized to further understand HIV-1 biology and to create a global vaccine. We discuss the impact of these approaches on vaccine development for other diseases, including COVID-19, influenza, and Zika virus. Additionally, we highlight the specific limitations faced with each approach and present the methods researchers employ to overcome these challenges. These innovative techniques, which have demonstrated preclinical and clinical success, have advanced the field closer to the ultimate goal of developing a global HIV-1 vaccine. Leveraging these advancements will enable significant strides in combating HIV-1 and other infectious diseases, ultimately improving global health outcomes. Full article

(This article belongs to the Special Issue Advances in HIV Vaccine Development)

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19 pages, 8275 KB

Open AccessEditor’s ChoiceArticle

Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses

by Wen-Chien Wang, Ekramy E. Sayedahmed, Marwa Alhashimi, Ahmed Elkashif, Vivek Gairola, Muralimanohara S. T. Murala, Suryaprakash Sambhara and Suresh K. Mittal

Vaccines 2025, 13(1), 95; https://doi.org/10.3390/vaccines13010095 - 20 Jan 2025

Cited by 5 | Viewed by 3567

Abstract

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were [...] Read more.

Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. Full article

(This article belongs to the Special Issue Advances in Vaccines Against Infectious Diseases)

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14 pages, 1446 KB

Open AccessEditor’s ChoiceArticle

Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults

by Geert Leroux-Roels, Robert L. Atmar, Jakob P. Cramer, Ian Escudero and Astrid Borkowski

Vaccines 2025, 13(1), 82; https://doi.org/10.3390/vaccines13010082 - 17 Jan 2025

Cited by 6 | Viewed by 3904

Abstract

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses [...] Read more.

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.4c. Serum antibodies and peripheral-blood antibody-secreting cells (ASCs) were measured. This report focuses on the single-dose 15/50 (µg GI.1/GII.4c) composition, which had been selected for further clinical development. Results: For single-dose 15/50 recipients (N = 105), GI.1-specific and GII.4c-specific histoblood-group antigen-blocking (HBGA) antibodies appeared to have persisted to 5 years, waning from a peak at 4 to 8 weeks, and plateauing above baseline after 3 years. From 3 to 5 years, GI.1-specific GMTs ranged between 53 (95%CI, 40–71) and 60 (95%CI, 46–77; N = 69–97) and were approximately 2-fold above the baseline GMT (24 (95%CI, 20–28); N = 105). GII.4c-specific GMTs ranged between 103 (95%CI, 77–138) and 114 (95%CI, 86–152; N = 70–97) and were above baseline, but by less than 2-fold (70 (95%CI, 53–92); N = 105). Similar kinetics were observed for pan-Ig titers and ASCs in a subset. Similar kinetics were also observed for HBGA and pan-Ig titers in recipients of other 15/50 dosages. Conclusions: Immune responses to HIL-214 in adults appear to persist for five years. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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15 pages, 272 KB

Open AccessEditor’s ChoiceReview

Pertussis Vaccination for Adults: An Updated Guide for Clinicians

by Kay Choong See

Vaccines 2025, 13(1), 60; https://doi.org/10.3390/vaccines13010060 - 11 Jan 2025

Cited by 12 | Viewed by 11340

Abstract

Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Although traditionally associated with children, pertussis is increasingly prevalent among adults, particularly those with comorbidities or weakened immune systems, where it can lead to severe [...] Read more.

Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Although traditionally associated with children, pertussis is increasingly prevalent among adults, particularly those with comorbidities or weakened immune systems, where it can lead to severe complications. Diagnosing pertussis in adults can be challenging due to its nonspecific symptoms, underreporting, and the limited sensitivity of available diagnostic tests. While treatment with macrolides is generally effective, it may not significantly alter the clinical course of the disease, and growing concerns about macrolide resistance are emerging. Vaccination remains the cornerstone of prevention, offering proven immunogenicity, efficacy, and safety. However, vaccination uptake remains low, partly due to limited patient awareness and insufficient prioritization by healthcare professionals. This review aims to provide clinicians with critical insights into pertussis epidemiology, vaccination strategies, and the latest guideline recommendations, empowering them to engage in meaningful discussions with adult patients and advocate for increased vaccination to combat this often-overlooked infection. Full article

(This article belongs to the Special Issue Vaccination Uptake and Public Health)

18 pages, 2085 KB

Open AccessEditor’s ChoiceReview

Lipoprotein Signal Peptide as Adjuvants: Leveraging Lipobox-Driven TLR2 Activation in Modern Vaccine Design

by Muhammad Umar, Haroon Afzal, Asad Murtaza and Li-Ting Cheng

Vaccines 2025, 13(1), 36; https://doi.org/10.3390/vaccines13010036 - 2 Jan 2025

Cited by 6 | Viewed by 5102

Abstract

Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these [...] Read more.

Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these proteins. The lipidation process is essential for TLR2 recognition and the activation of robust immune responses, positioning lipidated bacterial proteins as potent immunomodulators and adjuvants for vaccines against bacterial-, viral-, and cancer-related antigens. The structural diversity and cleavage pathways of bacterial SPs are critical in determining lipidation efficiency and protein localization, influencing their immunogenic potential. Recent advances in bioinformatics have significantly improved the prediction of SP structures and cleavage sites, facilitating the rational design of recombinant lipoproteins optimized for immune activation. Moreover, the use of SP-containing lipobox motifs, as adjuvants to lipidate heterologous proteins, has expanded the potential of vaccines targeting a broad range of pathogens. However, challenges persist in expressing lipidated proteins, particularly within heterologous systems. These challenges can be addressed by optimizing expression systems, such as engineering E. coli strains for enhanced lipidation. Thus, lipoprotein signal peptides (SPs) demonstrate remarkable versatility as adjuvants in vaccine development, diagnostics, and immune therapeutics, highlighting their essential role in advancing immune-based strategies to combat diverse pathogens. Full article

(This article belongs to the Special Issue State-of-the-Art Vaccine Design)

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15 pages, 5522 KB

Open AccessEditor’s ChoiceArticle

Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against Clostridioides difficile Infection

by Shaohui Wang, Joshua Heuler, Jessica Bullock, Junling Qin, Soumyadeep Chakraborty, Agbendeh Lubem Nathaniel, Shifeng Wang and Xingmin Sun

Vaccines 2025, 13(1), 21; https://doi.org/10.3390/vaccines13010021 - 30 Dec 2024

Cited by 10 | Viewed by 2574

Abstract

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high [...] Read more.

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. Full article

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16 pages, 615 KB

Open AccessEditor’s ChoiceReview

Durability of Adaptive Immunity in Immunocompetent and Immunocompromised Patients Across Different Respiratory Viruses: RSV, Influenza, and SARS-CoV-2

by Achilleas Livieratos, Lars Erik Schiro, Charalambos Gogos and Karolina Akinosoglou

Vaccines 2024, 12(12), 1444; https://doi.org/10.3390/vaccines12121444 - 22 Dec 2024

Cited by 5 | Viewed by 5727

Abstract

Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives [...] Read more.

Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives included examining humoral and cellular immune responses and exploring the impact of booster doses and hybrid immunity on extending protection. Methods. A literature review was conducted focusing on studies published from January 2014 to November 2024. The search targeted adaptive immunity post-vaccination, natural immunity, and hybrid immunity for SARS-CoV-2, influenza, and RSV. Selection criteria emphasized human populations, adaptive immunity outcomes, and immunocompromised individuals. The PICO framework guided the analysis, culminating in a detailed review of 30 studies. Results. SARS-CoV-2 vaccines exhibited robust initial antibody responses, which waned significantly within six months, necessitating frequent boosters. Influenza and RSV vaccines similarly showed declines in immunity, though some influenza vaccines demonstrated moderate durability. Hybrid immunity, arising from combined natural infection and vaccination, provided more resilient and lasting protection than vaccination alone, especially against emerging variants. Immunocompromised individuals consistently exhibited reduced durability in adaptive immune responses across all studied viruses. Challenges include rapid viral mutations, limiting the broad protection of current vaccines. Conclusions. Immune durability varies significantly across virus types and patient populations. Frequent boosters and hybrid immunity are critical to optimizing protection, particularly for vulnerable groups. The findings underscore the need for adaptable vaccination strategies and advancements in vaccine design to counter rapidly mutating respiratory pathogens effectively. Full article

(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)

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8 pages, 447 KB

Open AccessEditor’s ChoiceArticle

Immunoprophylaxis with MV140 Is Effective in the Reduction of Urinary Tract Infections—A Prospective Real-Life Study

by Filipe Abadesso Lopes, Miguel Miranda, André Ye, Joana Rodrigues, Paulo Pé-Leve, José Palma Reis and Ricardo Pereira e Silva

Vaccines 2024, 12(12), 1426; https://doi.org/10.3390/vaccines12121426 - 18 Dec 2024

Cited by 8 | Viewed by 6009

Abstract

Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. [...] Read more.

Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. This study aims at assessing the effectiveness of treatment with MV140 in a cohort of Portuguese patients presenting with recurrent UTIs. Methods: Prospective observational real-life study of 125 patients with complicated and uncomplicated recurrent UTIs treated with MV140. The primary outcome was a reduction in frequency and severity of UTIs after a follow-up of 12 months. Overall satisfaction, adverse events, and assessment of the effectiveness of MV140 in subgroups of patients with specific risk factors for UTIs were secondary outcomes. Results: In the 12 months after treatment outset, 38% of patients were UTI-free, 34% reported 1 or 2 UTI episodes, and the remaining 28% presented 3 or more UTIs, corresponding to a mean reduction of 3.20 (2.87–3.53, 95% C.I.; p < 0.001) UTI episodes per year per patient. The effectiveness of MV140 was the same regardless of sex, BMI, regular sexual activity, hypertension, diabetes mellitus, depression, paraplegia, performance of intermittent self-catheterization, indwelling bladder catheter, or previous use of other UTI-preventing vaccines. We observed a higher effectiveness in post-menopausal women compared to pre-menopausal (74.7% vs. 59.4%, respectively, p = 0.029). A total of 73% of patients reported a reduction in symptom severity or days of disease, and the mean global satisfaction was 7.52/10. Conclusions: MV140 demonstrated to be effective in the reduction rate of recurrent UTIs in a cohort of adult Portuguese patients. Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

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20 pages, 9291 KB

Open AccessEditor’s ChoiceArticle

Development Using Bioluminescence Imaging of a Recombinant Anguillid Herpesvirus 1 Vaccine Candidate Associated with Normal Replication In Vitro but Abortive Infection In Vivo

by Haiyan Zhang, Arun Sridhar, Natacha Delrez, Bo He, Sophie Fourny, Yuan Gao, Owen Donohoe and Alain F. C. Vanderplasschen

Vaccines 2024, 12(12), 1423; https://doi.org/10.3390/vaccines12121423 - 17 Dec 2024

Cited by 3 | Viewed by 2453

Abstract

Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic [...] Read more.

Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic loss within the eel aquaculture sector. To date, no vaccines are available against AngHV-1. Recently, we developed a safe and efficacious live attenuated recombinant vaccine against Cyprinid herpesvirus 3 (CyHV-3). This CyHV-3 recombinant vaccine encodes a deletion of ORF57. Orthologues of CyHV-3 ORF57 exist in Cyprinid herpesvirus 2 (CyHV-2, ORF57) and AngHV-1 (ORF35). Methods: In the present study, using recombinant strains and bioluminescent in vivo imaging, we investigated the effect of AngHV-1 ORF35 deletion on virus replication in vitro, virulence in vivo, and the potential of an AngHV-1 ORF35-deleted recombinant as a vaccine candidate for the mass vaccination of eels by immersion. With this goal in mind, we produced ORF35-deleted recombinants using two parental strains: a UK strain and a recombinant derived from the former strain by insertion of a Luciferase–GFP reporter cassette into a non-coding intergenic region. Results: Analyses of ORF35-deleted recombinants led to the following observations: (i) AngHV-1 ORF35 is not essential for viral growth in cell culture, and its deletion does not affect the production of extracellular virions despite reducing the size of viral plaque. (ii) In contrast to what has been observed for CyHV-3 ORF57 and CyHV-2 ORF57, in vivo bioluminescent analyses revealed that AngHV-1 ORF35 is an essential virulence factor and that its deletion led to abortive infection in vivo. (iii) Inoculation of the AngHV-1 ORF35-deleted recombinant by immersion induced a protective immune response against a wild-type challenge. This protection was shown to be dose-dependent and to rely on the infectivity of AngHV-1 ORF35-deleted virions. Conclusions: This study suggests that the AngHV-1 ORF35 protein has singular properties compared to its orthologues encoded by CyHV-2 and CyHV-3. It also supports the potential of AngHV-1 ORF35-deleted recombinants for the mass vaccination of eels by immersion. Full article

(This article belongs to the Special Issue Animal Herpesviruses)

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15 pages, 1318 KB

Open AccessEditor’s ChoiceReview

The Strategic Advisory Group of Experts (SAGE) on Immunization—Past, Present and Future

by Melanie Marti, Hanna Nohynek, Philippe Duclos, Katherine L. O’Brien and Joachim Hombach

Vaccines 2024, 12(12), 1402; https://doi.org/10.3390/vaccines12121402 - 12 Dec 2024

Cited by 12 | Viewed by 10966

Abstract

Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. [...] Read more.

Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. It further outlines the processes and methods currently used by SAGE and highlights some of its major achievements. Results: SAGE’s global policies have driven action toward eradication, elimination and disease control and addressed the optimization of vaccination and immunization. In total, 27 major policy positions on vaccines/vaccine-preventable diseases have guided global public health. During times of epidemics and pandemics, interim recommendations issued by SAGE have responded iteratively in real-time to provide evidence-driven response policies. SAGE is an adaptive advisory group that has modified its procedures and working approaches to meet the evolving challenges in public health and stay up-to-date with evolving scientific and guideline development standards. Conclusions: Over the last quarter century, SAGE has significantly contributed to shaping the immunization landscape. It has achieved and maintained a high level of integrity and credibility. The advisory group continues to be an authority in global public health, and its recommendations have profound implications for the health of individuals and populations across the globe. Full article

(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)

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24 pages, 1824 KB

Open AccessEditor’s ChoiceArticle

Safety, Immunogenicity, and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandavirus

by Philip Hicks, Tomaz B. Manzoni, Jonna B. Westover, Raegan J. Petch, Brianne Roper, Brian B. Gowen and Paul Bates

Vaccines 2024, 12(12), 1403; https://doi.org/10.3390/vaccines12121403 - 12 Dec 2024

Cited by 10 | Viewed by 3852

Abstract

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite [...] Read more.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar^−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar^−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar^−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile. Full article

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